Infection with Chlamydia pneumoniae (C. pneumoniae) is associated with an increased risk of cerebrovascular disease in the general population. Children with sickle cell anemia (SCA) are 200 times more likely to have cerebrovascular disease than normal children and are known to have an altered immune response to many infectious pathogens. C. pneumoniae is the leading infectious cause of acute chest syndrome which, interestingly, is a well- established risk factor for stroke in children with SCA. Our preliminary data indicates that SCA patients with MRI-documented cerebral infarction are 12 times more likely to have C. pneumoniae infection than SCA patients with normal MRI scans. We hypothesize that SCA patients have an abnormal immune response to C. pneumoniae that results in persistent infection which, in turn, triggers the development of cerebrovascular disease. Sickle cell anemia patients with an elevated velocity on transcranial doppler ultrasound (TCD) are known to be at high risk to develop stroke and an elevated TCD likely reflects underlying vascular disease. In addition, the Stroke Prevention in Sickle Cell Anemia Trial (STOP) demonstrated that almost 40% of children with an elevated TCD have evidence of cerebral infarction on MRI. Children with abnormal TCDs are, therefore, an appropriated population to investigate an association between cerebrovascular disease and C. pneumoniae infection. As an ancillary study of the STOP II trial we propose 1) To determine if C. pneumoniae infection is associated with cerebral infarction in children with SCA; 2) To characterize the immunological response to C. pneumoniae infection in patients with SCA. Establishing a link between C. pneumoniae infection and cerebral infarction will open the door to novel, less toxic approaches to the treatment and prevention of stroke in SCA, including antibiotics and vaccines. The data gained in this proposal would provide the preliminary data necessary to justify further clinical trials.